Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia

Jong Hun Lee; Seung-Gul Kang; Young-Min Park; Heon-Jeong Lee; Seog Ju Kim; Leen Kim

doi:10.0000/kjsr.2012.15.1.34

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Lee, Kang, Park, Lee, Kim, and Kim: Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia

Original Article

Korean Journal of Schizophrenia Research

Korean Journal of Schizophrenia Research 2012; 15(1): 34-38.

Published online: 30 June 2012

DOI: https://doi.org/10.0000/kjsr.2012.15.1.34

Association Study between Tryptophan Hydroxylase 2 Gene -703G/T Polymorphism and Tardive Dyskinesia

Jong Hun Lee, MD, PhD¹, Seung-Gul Kang, MD, PhD², Young-Min Park, MD, PhD³, Heon-Jeong Lee, MD, PhD⁴, Seog Ju Kim, MD, PhD⁵, Leen Kim, MD, PhD⁴

¹Department of Psychiatry, Catholic University of Daegu, College of Medicine, Daegu, Korea.

²Department of Psychiatry, Gachon University School of Medicine, Incheon, Korea.

³Department of Psychiatry, Inje University College of Medicine, Goyang, Korea.

⁴Department of Psychiatry, Korea University College of Medicine, Seoul, Korea.

⁵Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.

Address for correspondence: Heon-Jeong Lee, Department of Psychiatry, Korea University College of Medicine, Anam-dong 5-ga, Seongbuk-gu, Seoul 136-705, Korea. Tel: 02-920-6721, Fax: 02-929-7679, leehjeong@korea.ac.kr

Received 26 March 2012 Revised 25 April 2012 Accepted 10 May 2012

Abstract

Objectives

Tardive dyskinesia (TD) is a serious and sometimes irreversible adverse effect that may develop during long-term antipsychotics treatment. Previous studies have suggested that brain serotonergic systems are related to TD vulnerability and tryptophan hydroxylase (TPH) is the rate limiting enzyme in the biosynthesis of serotonin. This study aimed to investigate the association between TPH2 gene -703G/T polymorphism (rs4570625) and antipsychotic-induced TD in the Korean schizophrenia patients.

Methods

We investigated whether TPH2 gene -703G/T polymorphism is associated with antipsychotic-induced TD in 280 Korean schizophrenia patients. The subjects with TD (n=105) and without TD (n=175) were matched for antipsychotic drug exposure and other relevant variables.

Results

There was no significant difference in the distribution of genotypic (χ²=3.00, p=0.223) and allelic (χ²=0.19, p=0.661) frequencies between patients group with TD and without TD. There was no significant difference in total Abnormal Involuntary Movement Scale score (F=1.95, p=0.362) among the genotype groups, either.

Conclusions

The present study does not support that TPH2 gene -703G/T polymorphism is involved in TD of the Korean schizophrenia subjects.

Keywords: Tardive dyskinesia, Tryptophan hydroxylase 2 gene, Schizophrenia

Figures and Tables

Table 1

Comparison of the TPH2 -703G/T (rs4570625) genotype and allele frequencies between the schizophrenic patients with and without TD

TPH2 : Tryptophan Hydroxylase 2 Gene, TD : Tardive Dyskinesia

Table 2

Comparison of AIMS score and clinical variables among the TPH2 -703G/T (rs4570625) genotype groups

Values are given as mean±SD or n, AIMS : Abnormal Involuntary Movement Scale, TPH2: Tryptophan Hydroxylase 2 Gene, PANSS : Positive and Negative Syndrome Scale, ^aANCOVA test adjusted for age and treatment duration

References

1. Jeste DV, Caligiuri MP. Tardive dyskinesia. Schizophr Bull. 1993. 19:303–315.

2. Kane JM, Woerner M, Lieberman J. Tardive dyskinesia: prevalence, incidence, and risk factors. J Clin Psychopharmacol. 1988. 8:52S–56S.

3. Tarsy D, Baldessarini RJ. Epidemiology of tardive dyskinesia: is risk declining with modern antipsychotics? Mov Disord. 2006. 21:589–598.

4. Tamminga CA, Dale JM, Goodman L, Kaneda H, Kaneda N. Neuroleptic-induced vacuous chewing movements as an animal model of tardive dyskinesia: a study in three rat strains. Psychopharmacology (Berl). 1990. 102:474–478.

5. Yassa R, Ananth J. Familial tardive dyskinesia. Am J Psychiatry. 1981. 138:1618–1619.

6. Tarsy D, Baldessarini RJ. The pathophysiologic basis of tardive dyskinesia. Biol Psychiatry. 1977. 12:431–450.

7. Hsieh CJ, Chen YC, Lai MS, Hong CJ, Chien KL. Genetic variability in serotonin receptor and transporter genes may influence risk for tardive dyskinesia in chronic schizophrenia. Psychiatry Res. 2011. 188:175–176.

8. Casey DE, Gerlach J, Magelund G, Christensen TR. gamma-Acetylenic GABA in tardive dyskinesia. Arch Gen Psychiatry. 1980. 37:1376–1379.

9. Andreassen OA, Jorgensen HA. Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Prog Neurobiol. 2000. 61:525–541.

10. Lee HJ, Kang SG. Genetics of tardive dyskinesia. Int Rev Neurobiol. 2011. 98:231–264.

11. Meltzer HY. The role of serotonin in antipsychotic drug action. Neuropsychopharmacology. 1999. 21:106S–115S.

12. Schillevoort I, van Puijenbroek EP, de Boer A, Roos RA, Jansen PA, Leufkens HG. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports. Int Clin Psychopharmacol. 2002. 17:75–79.

13. Sandyk R, Bamford CR, Khan I, Fisher H. L-tryptophan in neuroleptic-induced tardive dyskinesia. Int J Neurosci. 1988. 42:127–130.

14. Basile VS, Ozdemir V, Masellis M, Meltzer HY, Lieberman JA, Potkin SG, et al. Lack of association between serotonin-2A receptor gene (HTR2A) polymorphisms and tardive dyskinesia in schizophrenia. Mol Psychiatry. 2001. 6:230–234.

15. Segman RH, Heresco-Levy U, Finkel B, Goltser T, Shalem R, Schlafman M, et al. Association between the serotonin 2A receptor gene and tardive dyskinesia in chronic schizophrenia. Mol Psychiatry. 2001. 6:225–229.

16. Tan EC, Chong SA, Mahendran R, Dong F, Tan CH. Susceptibility to neuroleptic-induced tardive dyskinesia and the T102C polymorphism in the serotonin type 2A receptor. Biol Psychiatry. 2001. 50:144–147.

17. Herken H, Erdal ME, Böke Ö, Savas HA. Tardive dyskinesia is not associated with the polymorphisms of 5-HT2A receptor gene, serotonin transporter gene and catechol-o-methyltransferase gene. Eur Psychiatry. 2003. 18:77–81.

18. Chong SA, Tan EC, Tan CH, Mahendren R, Tay AH, Chua HC. Tardive dyskinesia is not associated with the serotonin gene polymorphism (5-HTTLPR) in Chinese. Am J Med Genet. 2000. 96:712–715.

19. Kim YK, Yoon HK. Effect of serotonin-related gene polymorphisms on pathogenesis and treatment response in korean schizophrenic patients. Behav Genet. 2011. 41:709–715.

20. Zill P, Buttner A, Eisenmenger W, Moller HJ, Ackenheil M, Bondy B. Analysis of tryptophan hydroxylase I and II mRNA expression in the human brain: a post-mortem study. J Psychiatr Res. 2007. 41:168–173.

21. Patel PD, Pontrello C, Burke S. Robust and tissue-specific expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biol Psychiatry. 2004. 55:428–433.

22. De Luca V, Likhodi O, Van Tol HH, Kennedy JL, Wong AH. Tryptophan hydroxylase 2 gene expression and promoter polymorphisms in bipolar disorder and schizophrenia. Psychopharmacology (Berl). 2005. 183:378–382.

23. Lin YM, Chao SC, Chen TM, Lai TJ, Chen JS, Sun HS. Association of functional polymorphisms of the human tryptophan hydroxylase 2 gene with risk for bipolar disorder in Han Chinese. Arch Gen Psychiatry. 2007. 64:1015–1024.

24. Lopez VA, Detera-Wadleigh S, Cardona I, Kassem L, McMahon FJ. Nested association between genetic variation in tryptophan hydroxylase II, bipolar affective disorder, and suicide attempts. Biol Psychiatry. 2007. 61:181–186.

25. Al-Janabi I, Arranz MJ, Blakemore AI, Saiz PA, Susce MT, Glaser PE, et al. Association study of serotonergic gene variants with antipsychotic-induced adverse reactions. Psychiatr Genet. 2009. 19:305–311.

26. Segman RH, Goltser T, Heresco-Levy U, Finkel B, Shalem R, Schlafman M, et al. Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia. Pharmacogenomics J. 2003. 3:277–283.

27. Kim YK, Lee HJ, Yang JC, Hwang JA, Yoon HK. A tryptophan hydroxylase 2 gene polymorphism is associated with panic disorder. Behav Genet. 2009. 39:170–175.

28. Han OS, Hong JP. Structured Clinical Interview for DSM-IV Axis I Disorder-Korean Version. 2000. Seoul: Hana Medical Publishing.

29. Lee HJ, Kang SG, Choi JE, Paik JW, Kim YK, Kim SH, et al. No association between dopamine D4 receptor gene -521 C/T polymorphism and tardive dyskinesia in schizophrenia. Neuropsychobiology. 2007. 55:47–51.

30. Lee HJ, Kang RH, Lim SW, Paik JW, Choi MJ, Lee MS. No association between the brain-derived neurotrophic factor gene Val66Met polymorphism and post-traumatic stress disorder. Stress and Health. 2006. 22:115–119.

31. Lee HJ, Kang SG, Paik JW, Lee MS, Cho BH, Park YM, et al. No evidence for an association between G protein beta3 subunit gene C825T polymorphism and tardive dyskinesia in schizophrenia. Hum Psychopharmacol. 2007. 22:501–504.

32. Kang SG, Choi JE, An H, Lim SW, Lee HJ, Han C, et al. No association between the brain-derived neurotrophic factor gene Val66Met polymorphism and tardive dyskinesia in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2008. 32:1545–1548.

33. Kang SG, Choi JE, An H, Park YM, Lee HJ, Han C, et al. Manganese superoxide dismutase gene Ala-9Val polymorphism might be related to the severity of abnormal involuntary movements in Korean schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry. 2008. 32:1844–1847.

34. Kang SG, Choi JE, Park YM, Lee HJ, Han C, Kim YK, et al. Val158Met Polymorphism in the Catechol-O-Methyltransferase (COMT) Gene Is Not Associated with Tardive Dyskinesia in Schizophrenia. Neuropsychobiology. 2008. 57:22–25.

35. Kang SG, Lee HJ, Choi JE, An H, Rhee M, Kim L. Association study between glutathione S-transferase GST-M1, GST-T1, and GST-P1 polymorphisms and tardive dyskinesia. Hum Psychopharmacol. 2009. 24:55–60.

36. Park YM, Kang SG, Choi JE, Kim YK, Kim SH, Park JY, et al. No Evidence for an Association between Dopamine D2 Receptor Polymorphisms and Tardive Dyskinesia in Korean Schizophrenia Patients. Psychiatry Investig. 2011. 8:49–54.

37. Guy W. Abnormal Involuntary Movement Scale (AIMS). ECDEU assessment manual for psychopharmacology. 1976. Rev. ed. Rockville, MD: U.S. Dept. of Health, Education, and Welfare;534–537.

38. Schooler NR, Kane JM. Research diagnosis for tardive dyskinesia. Arch Gen Psychiatry. 1982. 39:486–487.

39. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987. 13:261–276.

40. Yoon HK, Kim YK. TPH2 -703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009. 33:403–409.

41. Lerer B, Segman RH, Tan EC, Basile VS, Cavallaro R, Aschauer HN, et al. Combined analysis of 635 patients confirms an age-related association of the serotonin 2A receptor gene with tardive dyskinesia and specificity for the non-orofacial subtype. Int J Neuropsychopharmacol. 2005. 8:411–425.

42. Al Hadithy AF, Ivanova SA, Pechlivanoglou P, Semke A, Fedorenko O, Kornetova E, et al. Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia. Prog Neuropsychopharmacol Biol Psychiatry. 2009. 33:475–481.

43. Wilffert B, Al Hadithy AF, Sing VJ, Matroos G, Hoek HW, van Os J, et al. The role of dopamine D3, 5-HT2A and 5-HT2C receptor variants as pharmacogenetic determinants in tardive dyskinesia in African-Caribbean patients under chronic antipsychotic treatment: Curacao extrapyramidal syndromes study IX. J Psychopharmacol. 2009. 23:652–659.

44. Segman RH, Heresco-Levy U, Finkel B, Inbar R, Neeman T, Schlafman M, et al. Association between the serotonin 2C receptor gene and tardive dyskinesia in chronic schizophrenia: additive contribution of 5-HT2Cser and DRD3gly alleles to susceptibility. Psychopharmacology (Berl). 2000. 152:408–413.

45. Zhang ZJ, Zhang XB, Sha WW, Reynolds GP. Association of a polymorphism in the promoter region of the serotonin 5-HT2C receptor gene with tardive dyskinesia in patients with schizophrenia. Mol Psychiatry. 2002. 7:670–671.

46. Deshpande SN, Varma PG, Semwal P, Rao AR, Bhatia T, Nimgaonkar VL, et al. II. Serotonin receptor gene polymorphisms and their association with tardive dyskinesia among schizophrenia patients from North India. Psychiatr Genet. 2005. 15:157–158.

47. Rietschel M, Naber D, Fimmers R, Moller HJ, Propping P, Nothen MM. Efficacy and side-effects of clozapine not associated with variation in the 5-HT2C receptor. Neuroreport. 1997. 8:1999–2003.

48. Han GR, Lee YW, Lee HL, Kim SM, Ku TW, Kang IH, et al. A Korean population study of the nine STR loci FGA, VWA, D3S1358, D18S51, D21S11, D8S1179, D7S820, D13S317 and D5S818. Int J Legal Med. 2000. 114:41–44.

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